Many central nervous system dysfunctions involve a disruption of synaptic transmission, although the locus of the problem is not always clear. In addition, normal synaptic transmission is essential for the long- term synaptic changes thought to underlie learning and memory. Quantal analysis of transmission at central synapses is a potentially powerful tool in the study of synaptic plasticity because it can measure and localize changes in synaptic strength. Most central neurons show variability in amplitudes of miniature EPSCs, which are thought to represent the postsynaptic response to one quantum, or the contents of a single synaptic vesicle. A presynaptic origin of quantal variability would imply that postsynaptic AMPA receptors are not saturated by one quantum; however, different groups have provided evidence supporting and opposing AMPA- receptor saturation. Receptor saturation and factors contributing to quantal variability at CNS synapses have important implications for measuring changes in synaptic strength. The proposed research examines three potential sources of quantal variability: the amount of glutamate released from one quantum, and changes in the number and single-channel behavior of postsynaptic AMPA receptors. In addition, this work will also investigate the effect that single-channel properties of postsynaptic AMPA receptors may have on estimates of the glutamate concentration in the synaptic cleft.